The objectives of the proposed investigations are to obtain a better understanding of the nature of lesions and processes leading to cell reproductive death, and to study the interrelationships of factors which influence radiosensitivity with an emphasis on their implications for radiotherapy. A quantitative comparison would be made of cell killing and chromosomal aberration production by fluorescent lamp irradiation following different schemes of BUdR incorporation using synchronous cell cultures. We plan to examine the intermediate development of damage to chromatin during interphase by inducing premature chromosome condensation (PCC) following a variety of different treatments. The nature of the G2 delay and a mitotic block produced by continuous irradiation with gamma-rays at low dose-rate will also be examined. In recent years, much attention has been given to the possible radiotherapeutic advantages of elaborate and expensive treatment modalities such as the use of neutrons, protons, or negative pi mesons, while very few workers have focused their attention toward understanding the successful use of low activity interstitial or intracavitary sources. The advantages of the latter may well involve dose-rate as well as dose distribution. We plan to continue studying the effects of dose-rate and multi-fraction acute dose regimes on the life cycle and survival of mammalian cells in culture. BIBLIOGRAPHIC REFERENCES: X-ray and U.V. induced chromatid aberrations: Evidence for polynemic chromosomes? Bender, M.A., Bedford, J.S., Griggs, H.G., and Merz, T., Mutation Research 28, 191-197, 1975. The estimation of survival at low doses and the limits of resolution of the single cell plating technique. Bedford, J.S. and Griggs, H.G., In: Cell Survival after Low Doses of Radiation: Proceedings of the Sixth L.H. Gray Conference, pp 34-39, The Institute of Physics and John Wiley and Sons Ltd. (1975).